Glomerulonephritis (mechanism of disease)

Summary

This video explains the pathophysiology, manifestations, and causes of glomerulonephritis, a kidney condition characterized by inflammation, glomerular damage, and leakage of proteins and red blood cells into the urine. Key symptoms include proteinuria, hematuria, hypertension, and edema. The video covers various causes, such as post-streptococcal infections, lupus, vasculitis, and genetic disorders like Alport syndrome. It also highlights distinct diagnostic features like low serum C3 levels, specific antibodies, and characteristic patterns seen in lab tests, including immunofluorescence and electron microscopy. The video concludes by addressing the risk of rapidly progressive glomerulonephritis, a severe form with poor prognosis.

Takeaways

• 😀 Glomerulonephritis (GN) is characterized by inflammation of the kidneys leading to glomerular capillary damage, resulting in leakage of proteins and red blood cells.
• 😀 Proteinuria (excess protein in urine) and hematuria (blood in urine) are key manifestations of GN, with possible severe cases showing dark, 'Coca-Cola' colored urine.
• 😀 GN causes a decreased glomerular filtration rate (GFR), which can lead to oliguria (low urine output) and azotemia (elevated nitrogenous waste in the blood).
• 😀 Fluid retention from low GFR results in hypertension and edema, often noticeable in the legs as pitting edema.
• 😀 Post-streptococcal GN is common in children (3-12 years), occurring weeks after a group A strep infection, often diagnosed by positive anti-strep antibodies and low serum C3.
• 😀 Diffuse proliferative GN is linked with lupus and IgA nephropathy, presenting with nephrotic syndrome and granular deposition on immunofluorescence microscopy.
• 😀 Small vessel vasculitis can lead to GN, with conditions like granulomatosis with polyangiitis (ANCA-associated), microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis.
• 😀 Goodpasture syndrome involves antibodies against the glomerular basement membrane, resulting in a type II hypersensitivity reaction and can be identified via immunofluorescence.
• 😀 Hereditary conditions like thin basement membrane nephropathy and Alport syndrome can also cause GN, with Alport syndrome presenting with hearing loss and eye issues.
• 😀 IgA nephropathy (Berger’s disease) is the most common idiopathic GN, marked by high IgA levels and normal C3, with characteristic mesangial proliferation seen on microscopy.
• 😀 Membranoproliferative GN in children presents with nephrotic syndrome and low serum C3, and is marked by a 'tram-track' appearance on light microscopy.
• 😀 Rapidly Progressive GN, characterized by crescent formations on microscopy, has a poor prognosis and can rapidly lead to end-stage renal disease, with the first six causes of GN potentially leading to this phenotype.

Q & A

What is the primary cause of glomerulonephritis?

Glomerulonephritis is primarily caused by inflammation in the kidneys, which leads to damage in the glomerular capillaries, resulting in leakage of proteins and red blood cells.

What are the key manifestations of glomerulonephritis?

The key manifestations include proteinuria (excess protein in urine), hematuria (blood in urine), red blood cell casts, oliguria (decreased urine output), azotemia (elevated nitrogenous compounds in blood), hypertension, and edema, particularly in the legs.

What distinguishes nephrotic syndrome from nephritic syndrome in glomerulonephritis?

Nephrotic syndrome is characterized by proteinuria greater than 3.5 grams per 24 hours, while nephritic syndrome is more focused on hematuria, oliguria, and a decreased GFR. Both can occur simultaneously but have distinct characteristics.

How does inflammation in the glomerular basement membrane affect kidney function?

Inflammation in the glomerular basement membrane causes it to become porous, allowing the leakage of proteins and red blood cells into the urine. This also reduces glomerular filtration rate (GFR), leading to decreased urine output and fluid retention, contributing to symptoms like edema and hypertension.

What causes the presence of red blood cell casts in urine?

Red blood cell casts are caused by the clumping of red blood cells in the renal tubules due to damage in the glomerular basement membrane, which results in the leakage of blood into the urine.

Which infection is most commonly associated with post-streptococcal glomerulonephritis?

Post-streptococcal glomerulonephritis is most commonly associated with a group A streptococcal infection, which may involve either the skin or throat.

What laboratory findings would indicate post-streptococcal glomerulonephritis?

Lab findings that indicate post-streptococcal glomerulonephritis include a positive anti-strep antibody test and low serum C3 levels. Immunofluorescence microscopy also shows depositions of IgG.

How is diffuse proliferative glomerulonephritis related to lupus?

Diffuse proliferative glomerulonephritis is commonly associated with lupus, a systemic autoimmune disease. It can present with nephrotic syndrome and is characterized by low serum C3 levels and granular deposits on immunofluorescence.

What is the distinguishing feature of eosinophilic granulomatosis with polyangiitis (EGPA)?

The distinguishing feature of eosinophilic granulomatosis with polyangiitis (EGPA) is the presence of eosinophilia, an elevated eosinophil count in the blood, which helps differentiate it from other types of microscopic polyangiitis.

What is the characteristic finding in the kidneys of patients with membranous glomerulonephritis?

The characteristic finding in membranous glomerulonephritis is the 'tram-track' appearance on light microscopy, which is a result of thickened glomerular capillary walls.

What is rapidly progressive glomerulonephritis, and how does it differ from other types of glomerulonephritis?

Rapidly progressive glomerulonephritis is a severe form of kidney inflammation that leads to crescent formation in the glomeruli. It typically has a poor prognosis, often resulting in end-stage renal disease within weeks. It can be caused by several conditions, including the first six types of glomerulonephritis, but the crescent formation is a key distinguishing feature.

How is Goodpasture syndrome diagnosed?

Goodpasture syndrome is diagnosed through the detection of antibodies against the glomerular basement membrane (type IV collagen) in the blood. Immunofluorescence microscopy shows these antibodies deposited in the kidneys.